Abstract
Naturally occurring cell death is common during lymphoid development and activation. The death of developing lymphoid cells is a highly regulated process that serves to select lymphoid populations that are functionally competent, and to remove cells that are not longer needed or potentially autoreactivel. Elimination of self-reactive B and T lymphocytes by apoptosis is thought to play a major role in the establishment of self-tolerance. The latter process is mediated by high avidity interactions between antigen receptors and self-antigens2. In contrast, signaling via the Fas receptor appears to play a major role in the elimination of activated lymphocytes during immune responses in peripheral tissues3. In addition, to the antigen and Fas receptors, survival of lymphocytes is controlled by certain cytokines and costimulatory signals4−5. The intracellular mechanism that regulates and executes the death program is still poorly understood but it is thought that cell death is controlled by a genetic program induced within the dying lymphocyte. Recently, several genes have been identified that appear to play critical roles in lymphoid survival6. The bc1-2 protooncogene was the first member of a growing family of genes that suppresses cell death in lymphoid cells7. Constitutive expression of bc1-2 in lymphoid cells prevents or delays apoptosis induced by multiple stimuli7. A role of Bc1-2 in T and B-cell biology was suggested by its highly restricted cellular distribution during development and in mature lymphoid populations8−9. Recent evidences suggest that Bc1-2 plays a role in positive selection of thymocytes 10−12. However, the ability of Bc1-2 to influence negative selection of thymocytes and immature B cells is controversial13−15.
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References
R.E. Ellis, J.Y. Yuang, and H.R. Horvitz, Mechanisms and functions of cell death. Annu. Rev. Cell. Biol. 7: 633 (1991).
G.J.V. Nossal, Negative selection of lymphocytes, Cell 76: 229 (1994).
D.R. Green and D.W. Scott, Activation-induced apoptosis in lymphocytes. Curr. Opin. Immunol. 6: 476 (1994).
H. Groux, D. Monte, B. Plouvier, A. Capron, and J.C. Ameisen, CD3-mediated apoptosis of human medullary thymocytes and activated peripheral T cells: respective roles of interleukin-1, interleukin-2, interferon-y and accessory cells, Eue J. Immunol. 23: 1623 (1993).
J. Hasbold, C. Johnson-Léger, C.J. Atkins, E.A. Clark, and G.G.B. Klaus, Properties of mouse CD40: cellular distribution of CD40 and B cell activation by monoclonal anti-mouse CD40 antibodies, Eur. J. Immunol. 24: 1835 (1994).
G.T. Williams and C.A. Smith, Molecular regulation of apoptosis: genetic controls on cell death, Cell 74: 777 (1993).
G. Nunez and M.F. Clarke, The Bc1–2 family of proteins: regulators of cell death and survival, Trends. Cell. Biol. 4: 399 (1994).
J. Gratiot-Deans, L. Ding, L. A. Turka, and G. Nunez, bcl-2 proto-oncogene expression during human T cell developmen. Evidence for biphasic regulation. J. Immunol. 151: 83 (1993).
R. Merino, L. Ding, D.J. Veis, S.J. Korsmeyer, and G. Nunez, Developmental regulation of the Bc1–2 protein and susceptibility to cell death in B lymphocytes, EMBO J. 13: 683 (1994).
A. Strasser, A.W. Harris, H. von Boehmer, and S. Cory, Positive and negative selection of T cells in T-cell receptor transgenic mice expressing a bc1–2 transgene, Proc. Natl. Acad. Sci. USA 91: 1376 (1994).
G.P. Linette, M.J. Grusby, S.H. Hedrick, T.H. Hansen, L.H. Glimcher, and S.J. Korsmeyer, Bcl-2 is upregulated at the CD4+CD8+ stage during positive selection and promotes thymocyte differentiation at several control points, Immunity 1:197 (1994).
J. Gratiot-Deans, R. Merino, G. Nunez, and L.A. Turka, Bc1–2 expression during T-cell development: Early loss and late return occur at specific stages of commitment to differentiation and survival, Proc. Natl. Acad. Sci.91:10685 (1994).
C.L. Sentman, J.R. Shutter, D. Hockenbery, O. Kanagawa, and S.J. Korsmeyer, bc1–2 inhibits multiple forms of apoptosis but not negative selection in thymocytes, Cell 67: 87 (1991).
A. Strasser, A., A.W. Harris, and S. Cory, bc1–2 transgene inhibits T cell death and perturbs thymic self-censorship, Cell 67: 889 (1991).
R.M. Siegel, M. Katsumata, T. Miyashita, D.C. Louie, M.I. Greene, and J.C. Reed, Inhibition of thymocyte apoptosis and negative selection in transgenic mice, Proc. Natl. Acad. Sci. USA 89: 7003 (1992).
D.J. Veis, C.M. Sorenson, J.R. Shutter, and S.J. Korsmeyer, Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys. and hypopigmented hair, Cell 75: 229 (1993).
K. Nakayama, K. Nakayama, I. Negishi, K. Kuida, Y. Shinkai, M.C. Louie, L.E. Fields, P.J. Lucas, V. Stewart, F.W. Alt, and D.Y. Loh, Disappearance of the lymphoid system in Bcl-2 homozygous mutant chimeric mice, Science 261: 1584 (1993).
L.H. Boise, M. Gonzalez-Garcia, C.E. Postema, L. Ding, T. Linsten, L.A. Turka, X. Mao, G. Nunez, and C.B. Thompson, bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death, Cell 74: 597 (1993).
A.R. Gottschalk, L.H. Boise, C.B. Thompson, and J. Quintans, Identification of immunosuppressant-induced apoptosis in a murine B-cell line and its prevention by bcl-x but not bc1–2. Proc. Natl. Acad. Sci. USA 92: 7350 (1994).
M. Gonzalez-Garcia, R. Perez-Ballestero, L. Ding, L. Duan., L.H. Boise, C.B. Thompson, and G. Nunez, Bcl-xL is the major Bc1-x mRNA form expressed during murine development and its product localizes to the outer mitochondria, Development 120: 3033 (1994).
W. Fang, J.J. Rivard, D.L. Mueller, and T.W. Behrens, Cloning and molecular characterization of mouse bc1-x in B and T lymphocytes, J. Immunol. 153: 4388 (1994).
N. Motoyama, F. Wang, K.A. Roth, H. Sawa, K.-i. Nakayama, K. Nakayama, I. Negishi, S. Senju, Q. Zhang, S. Fujii, and D.Y. Loh, Massive cell death of immature hematopoietic cells and neurons in Bcl-x-deficient mice, Science 267: 1506 (1995).
A. Ma, J.C. Pena, B. Chang, E. Margosian, L. Davidson, F.W. Alt, and C.B. Thompson., Bclx regulates the survival of double-positive thymocytes, Proc. Natl. Acad. Sci. USA 92: 4763 (1995).
D.A.M. Grillot, R. Merino, J.C. Pena, W.C. Fanslow, F.D. Finkelman, C.B. Thompson, and G. Nrínez, bcl-x Exhibits regulated expression during B-cell development and activation, and modulates lymphocyte survival in transgenic mice, J. Exp. Med. 183: 1852 (1996).
D.A.M. Grillot, R. Merino and G. Nunez, bcl-x L displays a restricted expression during thymic development and inhibits multiple forms of apoptosis but not clonal deletion, J. Exp. Med. 182: 1973 (1995).
E. Yang, J. Zha, J. Jockel, L.H. Boise, C.B. Thompson, and S.J. Korsmeyer, Bad, a heterodimeric partner for Bcl-xL and Bcl-2, displaces Bax and promotes cell death, Cell 80: 285 (1995).
K. Nakayama, L.B. Dustin, and D.Y. Loh, T-B cell interaction inhibits spontaneous apoptosis of mature lymphocytes in Bcl-2-deficient mice, J. Exp. Med. 182: 1101 (1995).
L.H. Boise, A.J. Minn, P.J. Noel, C.H. June, M.A. Accavitti, T. Lindsten, and C.B. Thompson, CD28 costimulation can promote T cell survival by enhancing the expression of Bcl-XL, Immunity, 3: 87 (1995).
L.G. Radvanyi, Y. Shi, H. Vaziri, A. Sharma, R. Dhala, G.B. Mills, and R.G. Miller, CD28 costimulation inhibits TCR-induced apoptosis during a primary T cell response, J. Immunol. 156: 1788 (1996).
D.L. Mueller, S. Seiffert, W. Fang and T.W. Behrens, Differential regulation of bc1–2 and bcl-x by CD3, CD28, and the IL-2 receptorin cloned CD4’ helper T cells: a model for the long term survival of memory cells. J. Immunol. 156: 1764 (1996).
P. Kisielow, H. Bluthmann, U.D. Staerz, M. Steinmetz, and H. von Boehmer, Tolerance in T-cell receptor transgenic mice involves deletion of non mature CD4’CD8’thymocytes, Nature 333: 742 (1988).
J. Hasbold and G.G.B. Klaus, Anti-immunoglobulin antibodies induce apoptosis in immature B cell lymphomas. Eur. J. Immunol. 20: 1685 (1990).
R. Merino, D.A. M. Grillot, P.L. Simonian, S. Muthukkumar, W.C. Fanslow, S. Bondada, and G. Nunez, Modulation of anti-gM-induced apoptosis by Bcl-xL and CD40 in WEHI-231 cells. Dissociation from cell cycle arrest and dependence on the avidity of the antibody-IgM receptor interaction. J. Immunol. 155: 3830 (1995).
M.S.K. Choi, L.H. Boise, A.R. Gottschalk, J. Quintans, C.B. Thompson, and G.G.B. Klaus, The role of bcl-XL in CD40-mediated rescue from anti-µ-induced apoptosis in WEHI-231 B lymphoma cells, Eur. J. Immunol. 25: 1352 (1995).
T. Ishida, N. Kobayashi, T. Tojo, S. Shida, T. Yamamoto, and J.I. Inoue, CD40 signaling-mediated induction of Bcl-XL, Cdk4, and Cdk6. Implication of their cooperation in selective B cell growth. J Immunol. 155: 5527 (1995).
Z. Wang, J.G. Karras, R.G. Howard, and T.L. Rothstein, Induction of bcl-x by CD40 engagement rescues slg-induced apoptosis in murine B cells, J. Immunol. 155: 3722 (1995).
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Nuñez, G., Merino, R., Simonian, P.L., Grillot, D.A.M. (1996). Regulation of Lymphoid Apoptosis by Bcl-2 and Bcl-xL . In: Gupta, S., Cohen, J.J. (eds) Mechanisms of Lymphocyte Activation and Immune Regulation VI. Advances in Experimental Medicine and Biology, vol 406. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-0274-0_8
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